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and bone.  In  recent  years,  porcine  collagen has been   and glutaraldehyde makes Cosmoplast® less prone to
           marketed as an intradermal filler under the brand name of   degradation. Cosmoplast® is used for the treatment  of
           Evolence™ (ColBar LifeScience Ltd., Herzliya, Israel). Studies   deeper wrinkles and deep scars whereas Cosmoderm® is
           involving human medical devices have shown that porcine   used for the treatment  of superficial wrinkles, both with
                                                                                       [20]
           collagen is less immunogenic than bovine collagen, although   effects lasting for 3-7 months.  The Inamed clinical study of
           the amount of published data regarding its potential as   human collagen immunogenicity concluded with a 95% upper
                                                 [10]
           intradermal filler is still relatively insignificant.  In a phase   confidence interval that the probability of a hypersensitivity
           I clinical trial with 12 patients receiving  treatment  for   reaction from either Cosmoplast® or Cosmoderm® is less
           nasolabial folds, both Evolence™ and Zyplast® were found   than 1.3%.
                                                                       [21]
           to be safe and effective.  The degree of improvement in
                               [10]
           wrinkles, graded by blinded examiners,  was observed to   AlloDerm is a sheet derived from human dermis that requires
           be  much  greater  for Evolence™  at  both  the  6-month  and   a multi-step treatment to ensure optimal efficacy. Cymetra®
           18-month visiting periods.  A larger randomized, double-  (LifeCell Corp., Branchburg, NJ, U.S.A.) is an injectable
                                 [11]
           blinded trial found no significant difference in effectiveness   form of AlloDerm.  Very few trials have been conducted
                                                                              [22]
           between Evolence™ and NASHA (Restylane®) in the     comparing human-derived collagen  with  other  types  of
           treatment  of nasolabial folds at  the  6-month  assessment.   fillers. A randomized trial comparing Zyplast® (bovine
           Although there were no positive skin tests against porcine   collagen) and Cymetra® (human collagen) injections to the
           collagen, 6.1% of patients developed  IgG antibodies to   upper lip showed that Cymetra® had a much higher post-
           porcine  collagen. Although there  were  immunogenic   treatment value than Zyplast® by the 12-month visit, with
           reactions, it is important to note that none of them were   bruising being the most commonly observed adverse effect
                                                                            [23]
           considered to be adverse in nature. [12]            for both fillers.  Because Cymetra®  is  of human origin,
                                                               skin testing is not required prior to use.
           Another  study  was  conducted comparing  the  safety  and
           efficacy of TheraFill®, a porcine collagen filler, to a bovine   Although collagen treatment  is beneficial for most
           collagen filler for the treatment of nasolabial folds. In total 61   individuals, it has its limitations. Patients who are sensitive
           patients were evaluated in this randomized, double-blinded   to bovine collagen must instead use human collagen, which
           and split-face study over a 12-month period. The Wrinkle   is typically more expensive. Individuals with autoimmune
           Severity Rating Scale (WSRS) rating of TheraFill® was shown   diseases should completely avoid the use of foreign collagen.
           to be higher than that of bovine collagen filler by a small   Finally, the results typically last for a short period of time as
           margin, although not enough to be considered statistically   the body absorbs external collagen naturally.
           significant. Both fillers were similarly effective and safe
           without eliciting severe adverse reactions, suggesting that   Hyaluronic acid
           TheraFill® could suitably replace bovine collagen filler. [13]  HA is a very commonly found  substance which is usually
                                                               derived from either bacteria or rooster combs for use as an
           Many studies have been performed which assess the efficacy   intradermal filler.  Although several products containing
                                                                              [24]
           of bovine and porcine dermal fillers. The aforementioned   HA-related proteins  have shown a theoretical risk of
           studies discuss the adverse/allergic responses and  the   hypersensitivity,  there  is  no requirement  for skin testing
           efficacy of treatment  provided by these fillers. [14,15]  More   prior to use. [24]
           comparative studies  have  been  done  between  bovine  or
           porcine and  other fillers to choose  the safest and most   Restylane®, a type of non-animal stabilized hyaluronic
           preferred treatment.  With the advent of new technology,   acid (NASHA), is a stable, partially cross-linked form of HA.
                            [16]
           the cosmetic industry has moved on to various other types   It is fermented by bacteria and has a long track record of
           of intradermal fillers including human  collagen, smooth   safety (over 10 years) as an intradermal filler. Due to rapid
           gel hyaluronic acid, poly-L-lactic acid  (PLA), poly(methyl   degradation of hyaluronic acid  in  the  skin,  cross-linking
           methacrylate) (PMMA) microspheres, etc., which have proven   is required in order to produce a hydrophilic HA polymer.
           to be better alternatives to bovine and porcine fillers. These   Because no anesthetic is associated with Restylane®,
           are discussed in detail below.                      topical anesthesia  or a  nerve  block may  be  administered
                                                               prior to its use. Narins et al.  conducted a double-blinded,
                                                                                      [25]
           Human collagen                                      randomized, and longitudinal comparison study between
           Collagen has traditionally been extracted from animal sources   Restylane® and Zyplast® for treatment  of the nasolabial
           or cadavers. Recently researchers have proposed obtaining   fold.  In the study involving 138  patients, the Wrinkle
           human collagen from other sources including adipose tissue   Severity Rating Scale (WSRS) (with 1 being the lowest and
           obtained after  liposuction  and from  yeast  or bacteria   5 being the most severe) and Global Aesthetic Improvement
                                 [17]
           used for the production of recombinant human collagen.    Scale (GAIS) (on a scale of 5 ranging from “worse” to “very
                                                          [18]
           Moreover,  human  collagen can now also be  synthesized   much improved”) were  used at 2, 4, and 6 months  after
           in the lab as discovered by Raines.  Cosmoderm® and   baseline.  Both groups showed similar improvements  with
                                         [19]
           Cosmoplast® (Inamed Aesthetics) are some of the currently   90%  of patients exhibiting  improvement by 1 or 2 scores
           available products made of human collagen; both contain   according to the WSRS rating. At 6 months, more patients
           lidocaine and have received FDA approval. The collagen   showed improvement with Restylane® (56.9% for WSRS; 62%
           content is produced from a single human dermal fibroblast   for GAIS) than with Zyplast® (9.5% for WSRS; 8% for GAIS).
           cell line. Cross-linking between lysine residues on collagen   Reactions (e.g. swelling, tenderness, bruising, redness and
           Plast Aesthet Res || Vol 3 || Mar 23, 2016                                                          75
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